Our lab has identified an interesting relation between members of the Myc and E2f family of cell cycle regulators and chromatin changes and transcriptional regulation of differentiation of oligodendrocyte progenitors. We now propose to use primary cultures and genetic mouse models to test a new mechanistic model of oligodendrocyte differentiation. The results from the proposed experimental plan are likely to advance our knowledge not only in neural development and repair, but also in cancer and nuclear reprogramming and have wide implications for the development of novel therapeutic strategies. PUBLIC HEALTH RELEVANCE: The relationship between cell cycle and differentiation in progenitor cells is critical for a vast number of pathologies, ranging from cancer to repair. Although considerable progress has been made in the study of oncogenes in cellular transformation, still very little is known about their role in physiological conditions. This projet defines the role of Myc and E2F in the oligodendrocyte lineage and proposes a novel model of progenitor differentiation, linking cell cycle exit to chromatin condensation and transcriptional modulation.